This article presents a brief overview of the impact that antibiotic use in clinical medicine and in other settings, such as agriculture and animal farming, exerts on antimicrobial resistance. Resistance has been described to all antibiotics that are currently in use, and resistant strains were sometimes reported as soon as months after specific antibiotics became commercially available. There are many examples in which the increasing prevalence of resistant microbial strains jeopardized the continuing effective use of the respective antibiotics in clinical medicine. In addition to resistant infections that occur in health-care establishments, one of the recent challenges is the emergence of pathogens, such as MRSA, in the community, among individuals without any apparent risk factors for the infection. The transmission of resistant pathogens and antimicrobial resistance determinants across different components of the ecosystem transforms antibiotic resistance into a topic that extends beyond the scope of clinical medicine and needs to be visualized through an integrated global perspective that should incorporate a broad range of disciplines, including molecular genetics, microbiology, food science, ecology, agriculture, and environmental science. Understanding this complex multi- and interdisciplinary framework will enable the implementation of the most appropriate interventions toward determining the dynamics of antimicrobial resistance, limiting the emergence and spread of resistant strains, and ensuring the ongoing effective and safe use of antibiotics.